Rod-Shaped Liquid Plasticine Reactor: Advancing Photodynamic Therapy with Improved Light Absorption and Targeted ROS Delivery

Significance 

Photodynamic therapy (PDT) is a cutting-edge approach to treating cancer that harnesses the power of light to activate special drugs, called photosensitizers, directly at the tumor site. When exposed to light, these drugs release reactive oxygen species (ROS) that go to work, damaging cancer cells in a way that ideally leads to their destruction. PDT has some big advantages over traditional treatments like chemotherapy: it’s non-invasive, targets only the illuminated area, and typically comes with fewer side effects since it doesn’t affect the whole body. But despite its promise, PDT isn’t without its challenges. One of the biggest issues is that light doesn’t penetrate very deeply into tissue, which limits its reach, especially for tumors that aren’t right on the surface. Another problem is that ROS don’t always spread evenly, which means parts of the tumor can end up being missed, reducing the treatment’s overall effectiveness. Typically, in vitro studies of PDT systems use solid carriers to deliver these photosensitizers to the tumor. While these carriers are stable, they’re also quite rigid and don’t adapt well to tumors of different shapes and sizes. Plus, they tend to be closed structures, so the photosensitizers, ROS, and cancer cells aren’t able to interact as freely. This closed design makes it hard for ROS to reach every part of the tumor, leaving some cancer cells untreated. Another drawback is that solid carriers don’t always absorb light effectively, and since light absorption is key to generating enough ROS, this shortfall can prevent PDT from reaching its full potential. Recognizing these issues, Professor Xiaoguang Li’s team at Northwestern Polytechnical University developed a different kind of carrier for PDT: a flexible, rod-shaped liquid plasticine (LP) reactor. This LP reactor isn’t solid; it’s a semi-liquid structure, which makes it much more adaptable to the tumor’s shape and allows for better light exposure. Its open structure encourages more interaction with surrounding cells, which can make the ROS spread more effectively throughout the tumor. The rod shape is also an advantage, as it lines up better with the light source, allowing for deeper light penetration and more ROS generation. This design has the potential to provide more complete coverage, which may have significant implications for improving the efficacy of PDT and making PDT a more powerful and reliable option for treating cancer.

The researchers ran a series of experiments to see how well their new rod-shaped  LP reactor could enhance PDT compared to the usual methods. Their first focus was on how effectively the LP reactor could absorb light and produce ROS—the molecules that damage cancer cells during PDT. Because the LP reactor has a long, flexible, and open structure, it allowed for better interaction between the photosensitizers (the light-activated molecules) and nearby cells, unlike conventional, rigid setups that limit this contact. When they shone light on the LP reactor, it absorbed far more light, particularly along its long, rod-shaped structure, which aligned well with the light path. This design allowed the light to penetrate deeper, generating more ROS over a larger area and making the treatment more effective. By contrast, the conventional spherical carriers didn’t spread light as efficiently, meaning they generated less ROS and struggled to reach and impact target cells effectively. Next, the team wanted to see how well the LP reactor distributed ROS compared to traditional setups. They measured cell death rates between the rod-shaped LP reactor and the usual spherical liquid marble (LM) reactors to see which was more effective. When tested on cancer cell cultures, the LP reactor led to a much higher rate of cell death, suggesting that its unique shape helped sustain ROS production across a broader area. Its transparent, rod-like structure allowed light to spread evenly throughout, making it more effective at killing cancer cells. In contrast, the LM reactors produced fewer ROS, resulting in less cell destruction and a weaker treatment effect.

Temperature also played an important role in these tests. The authors used infrared imaging to track how heat built up within the LP reactor when exposed to light. The rod-shaped design allowed the light to focus in a way that created a concentrated area of warmth, which boosted ROS production even more. This heating effect was unique to the LP reactor and added another layer of effectiveness because warmer conditions can make cancer cells more vulnerable to ROS damage. The LM reactors, on the other hand, spread light in a less focused way, which led to less concentrated heat and, ultimately, a weaker impact on cancer cells. This difference in temperature distribution highlighted how the LP’s shape and structure really made a difference in delivering a stronger, more efficient PDT treatment. Finally, the researchers looked at how well the LP reactor performed at different depths—an important factor for any light-based therapy. They segmented the LP reactor and tested it across various lengths to simulate how light and ROS levels might change as the distance from the light source increased. The LP reactor consistently outperformed the spherical models at all distances, maintaining stable ROS levels and effectiveness even as the light source was positioned further away. This adaptability suggests that the LP reactor could be suitable for treating tumors of different sizes and depths, offering clear advantages over traditional closed systems by delivering a continuous and even spread of ROS throughout the treatment area.

This innovative research work of Professor Xiaoguang Li and colleagues has the potential to change how we use PDT for cancer treatment, addressing some of the key challenges that have held PDT back. Right now, traditional PDT methods have limitations—light doesn’t penetrate deeply enough, and the production of ROS which are critical for destroying cancer cells, isn’t always effective. These factors can make it hard for PDT to treat larger or deeper tumors thoroughly. The new rod-shaped LP reactor reported by Professor Xiaoguang Li offers an in vitro model around these problems. Its flexible, open design allows for far better light absorption and extends the reach of ROS. This means that PDT could potentially work on a much wider range of tumor sizes and depths, making treatments more consistent and reliable. But we think the impact of this research goes beyond just improving cancer treatment. The LP reactor’s adaptable, energy-efficient design holds significant potential for the development of various in vitro models tailored for medical treatments that rely on precise, light-driven reactions in a controlled environment. Because it generates ROS so effectively and manages heat well, this reactor could inspire similar designs for therapies targeting difficult-to-reach areas or for treatments that need longer-lasting effects. The LP reactor’s flexibility also facilitates the design of in vitro models aimed at advancing personalized treatment strategies, allowing doctors to tailor therapy to the specific characteristics of each patient’s tumor, which could make a significant difference in patient care. In setting a new standard for PDT system design, this study moves us toward much higher expectation on therapies that are not only more precise but also more adaptable to real-world challenges. With its ability to maintain effective ROS levels across different shapes and depths, the LP reactor could help to redefine light-based treatments, offering safer and more reliable options for patients. Its adaptable design could encourage further innovative research into other flexible, biocompatible materials, which could lead to even more advancements in minimally invasive cancer therapies.

Rod-Shaped Liquid Plasticine Reactor: Advancing Photodynamic Therapy with Improved Light Absorption and Targeted ROS Delivery - Medicine Innovates

About the author

Xiaoguang Li

Professor, Research direction leader of Shaanxi Liquid Physics Research Center
Northwestern Polytechnical University, China

I have focused on liquid manipulation since I got my PhD degree from Tongji University (China) in 2013, and my main interest lies in the production of structured liquids with solid-like shape plasticity as well as their applications in the biomedical arena. The structured liquids, as we call them liquid plasticines, are realized by encasing the liquids with hydrophobic particles. We have demonstrated that the liquid plasticines, serving as self-supporting liquid containers, are qualified for many biomedical tasks such as 3D cell culture, protein analysis, and tumor therapy, with unique advantages that are distinguished from conventional solid containers.

Reference

H. Liu, C. Peng, S. Guo, X. Liu, X. Li, Rod-Shaped Liquid Plasticine as Cuttable Minireactor for Photodynamic Therapy of Tumors. Small 2024, 20, 2309535.

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